BACKGROUND: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable. CASE PRESENTATION: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient. CONCLUSIONS: Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.

• Keywords
• Case report, Mesonephric-like adenocarcinoma, Ovary, Serous borderline tumor,
• MeSH
• Adenocarcinoma diagnosis   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesonephroma pathology   MeSH
• Biomarkers, Tumor analysis   MeSH
• Uterine Neoplasms diagnosis   pathology   MeSH
• Ovarian Neoplasms diagnosis   pathology   MeSH
• Ovary pathology   MeSH
• Precancerous Conditions pathology   MeSH
• Cystadenoma, Serous diagnosis   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

The most common histological subtypes of cutaneous melanoma include superficial spreading and nodular melanoma. However, the spectrum of somatic mutations developed in those lesions and all potential druggable targets have not yet been fully elucidated. We present the results of a sequence capture NGS analysis of 114 primary nodular and superficial spreading melanomas identifying driver mutations using biostatistical, immunohistochemical and/or functional approach. The spectrum and frequency of pathogenic or likely pathogenic variants were identified across 54 evaluated genes, including 59 novel mutations, and the newly identified TP53 loss-of-function mutations p.(L194P) and p.(R280K). Frequently mutated genes most commonly affected the MAPK pathway, followed by chromatin remodeling, and cell cycle regulation. Frequent aberrations were also detected in the genes coding for proteins involved in DNA repair and the regulation and modification of cellular tight junctions. Furthermore, relatively frequent mutations were described in KDR and MET, which represent potential clinically important targets. Those results suggest that with the development of new therapeutic possibilities, not only BRAF testing, but complex molecular testing of cutaneous melanoma may become an integral part of the decision process concerning the treatment of patients with melanoma.

• MeSH
• Cell Cycle genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Melanoma, Cutaneous Malignant MeSH
• MAP Kinase Signaling System genetics   MeSH
• Melanoma genetics   pathology   MeSH
• Young Adult MeSH
• Loss of Function Mutation genetics   MeSH
• Biomarkers, Tumor genetics   MeSH
• Tumor Suppressor Protein p53 genetics   MeSH
• Skin Neoplasms genetics   pathology   MeSH
• DNA Repair genetics   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Chromatin Assembly and Disassembly genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Tight Junctions genetics   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers, Tumor MeSH
• Tumor Suppressor Protein p53 MeSH
• Proto-Oncogene Proteins B-raf MeSH
• TP53 protein, human MeSH Browser